| First Author | Yao S | Year | 2015 |
| Journal | Nucleic Acids Res | Volume | 43 |
| Issue | 19 | Pages | 9362-78 |
| PubMed ID | 26446987 | Mgi Jnum | J:233869 |
| Mgi Id | MGI:5788237 | Doi | 10.1093/nar/gkv988 |
| Citation | Yao S, et al. (2015) MiRNA-891a-5p mediates HIV-1 Tat and KSHV Orf-K1 synergistic induction of angiogenesis by activating NF-kappaB signaling. Nucleic Acids Res 43(19):9362-78 |
| abstractText | Co-infection with HIV-1 and Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of aggressive AIDS-related Kaposi's sarcoma (AIDS-KS) characterized by abnormal angiogenesis. The impact of HIV-1 and KSHV interaction on the pathogenesis and extensive angiogenesis of AIDS-KS remains unclear. Here, we explored the synergistic effect of HIV-1 Tat and KSHV oncogene Orf-K1 on angiogenesis. Our results showed that soluble Tat or ectopic expression of Tat enhanced K1-induced cell proliferation, microtubule formation and angiogenesis in chorioallantoic membrane and nude mice models. Mechanistic studies revealed that Tat promoted K1-induced angiogenesis by enhancing NF-kappaB signaling. Mechanistically, we showed that Tat synergized with K1 to induce the expression of miR-891a-5p, which directly targeted IkappaBalpha 3' untranslated region, leading to NF-kappaB activation. Consequently, inhibition of miR-891a-5p increased IkappaBalpha level, prevented nuclear translocation of NF-kappaB p65 and ultimately suppressed the synergistic effect of Tat- and K1-induced angiogenesis. Our results illustrate that, by targeting IkappaBalpha to activate the NF-kappaB pathway, miR-891a-5p mediates Tat and K1 synergistic induction of angiogenesis. Therefore, the miR-891a-5p/NF-kappaB pathway is important in the pathogenesis of AIDS-KS, which could be an attractive therapeutic target for AIDS-KS. |
